Diagnosis and pharmacological management of Parkinson's - SIGN

Diagnosis anD Pharmacological management of Parkinson’s Disease
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Although the relative prevalence of dyskinesias with long term levodopa therapy may resemble
that of dopamine agonists, 68 there is evidence that patients treated with levodopa therapy for four
to six years have approximately a 40% likelihood of experiencing motor fluctuations and a 40%
risk of dyskinesias. 69 Alternative therapeutic agents are often employed as first line treatment to
delay starting levodopa and thereby reduce the onset of disabling dyskinesias.
Nausea and vomiting, common adverse effects of levodopa and DAs (see Annex 4), can be treated
with domperidone, a peripheral D2 antagonist in a dose of 10-20 mg three times daily. 70
a Patients with early Parkinson’s disease and motor symptoms may be considered for
treatment with levodopa in combination with a dopa decarboxylase inhibitor.
; The lowest effective dose of levodopa should be used to minimise the incidence of
adverse effects.
Impulse control disorders (ICDs) are uncommon with levodopa monotherapy. Pathological
gambling and other ICDs may occur with dopamine dysregulation syndrome (DDS) where
patients self escalate doses of levodopa and/or apomorphine to levels above those required
to control motor symptoms and patients with DDS often exhibit severe dyskinesia and ‘off’
period dysphoria. 71
; Surveillance for dopamine dysregulation syndrome should be undertaken in patients
receiving levodopa or intermittent apomorphine.
5.1.2 DOPAMINe AGONISTS
One meta-analysis, two systematic reviews and a number of RCTs have looked at the efficacy of
DAs in early PD. Overall, dopamine agonists improve the motor symptoms in early disease with
significant improvements in uPDRS total, motor, and activities of daily living (ADl) scores.
Randomised trials comparing the effectiveness of dopamine agonists with placebo in patients
with early PD have shown a significant improvement in uPDRS scores for agonist-treated
patients, in particular for part III motor examination scores. 72-77
A meta-analysis of DA therapy in patients with early PD included 29 RCTs involving 5,247
participants. 78 Dopamine agonists were associated with fewer motor complications compared
to levodopa but other important side effects were increased and people treated with agonists
were more likely to discontinue treatment due to adverse events (odds ratio OR 2.49, 95%
CI 2.08 to 2.98; p